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The retinal pigment epithelium cells grown from donated eye stem cells successfully treated retinal damage in macaques.

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Donor tissues provide the gift of sight

24 Dec 2021

A breakthrough stem cell transplant technology uses donated cadaver eyes to restore vision in patients with retinal degeneration.

Much of how we experience the world around us hinges on our ability to see clearly. Given how vital the sense of sight is, it may come as a surprise that vision is granted by a small, delicate, single layer of cells located at the back of the eyeballs.

The retinal pigment epithelium (RPE) serves many critical functions in the eye, including absorbing light, protecting against pathogens, and nourishing the light-sensitive receptors in the retina. Injury or damage to this fragile tissue causes blurring or vision loss.

Unfortunately, cell therapy approaches using transplanted human embryonic and induced pluripotent stem cells have yielded disappointing results in experimental models, with transplants only restoring RPE function for up to a month.

Xinyi Su, a Senior Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB), sought to look for alternative ways to extend the longevity of transplanted stem cells in patients with RPE damage. Collaborating with researchers at the Mount Sinai, New York, National University of Singapore’s (NUS) Yong Loo Lin School of Medicine, the Singapore Eye Research Institute and Duke-NUS Medical School, the team hypothesized that human RPE stem cell-derived RPE—or hRPESC-RPE, for short—holds promise as a novel cell therapy for RPE conditions.

“These stem cells, extracted from donated cadaver adult eyes, can be grown into RPE cells,” explained Su, adding that hRPESC-RPE could potentially serve as a limitless source of donor cells which could be profiled to ensure donor compatibility.

To test their theory, the team isolated hRPESC-RPE from adult cadaver eyes and maintained the cells under specialized cell culture conditions for a month. The researchers observed that these donor cells possessed stem cell-like characteristics, with the ability to divide into sheets of healthy, living RPE tissues.

Su and colleagues then tested whether these lab-grown hRPESC-RPE tissues could be used as viable therapies. Using a non-human primate model of RPE damage, they surgically transplanted hRPESC-RPE tissues into the eyes of macaques—reporting that transplanted human cells successfully integrated with the surrounding macaque tissues,

"These transplanted RPE patches were able to stably integrate for at least three months with no serious side effects,” said Su. “That’s three times longer than what other cell therapy approaches can achieve.”

These exciting results may pave the way for life-changing therapies for the 196 million people worldwide affected by age-related macular degeneration (AMD), a disease of the RPE.

Moving closer towards the clinical translation of this technology, the team has plans to demonstrate that hRPESC-RPE transplants can restore vision in non-human primate models of AMD. They are also building a preclinical data package to support an application to assess cell therapy in human clinical trials.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).

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References

Liu Z., Parikh, B.H., Tan, Q.S.W., Wong, D.S.L., Ong, K.H. et al. Surgical transplantation of human RPE stem cell-derived RPE monolayers into non-human primates with immunosuppression, Stem Cell Reports 16, 237-251 (2021) | article

About the Researcher

Xinyi Su is an A*STAR National Science Scholarship recipient who completed her medical and PhD degrees at the University of Cambridge, UK. She joined A*STAR’s Institute of Molecular and Cell Biology (IMCB) in 2016 and is currently a Principal Investigator. She still practices ophthalmology as a Consultant in vitreoretinal surgery at the National University Hospital, and holds an academic position as an Assistant Professor at the Department of Ophthalmology, National University of Singapore. Passionate about building bridges between science and medicine, Su’s interests lie in translational research for retinal therapeutics.

This article was made for A*STAR Research by Wildtype Media Group